EEG ANALYSIS OF DRUG REINFORCEMENT AND DEPENDENCE

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The endogenous opioid system plays an important role in maintaining level of arousal and sleep-wake rhythms. These mechanisms are also involved in the ability of opioids and other classes of abused substances to act as reinforcers for self-administration behavior. The overall goal of this project is to use quantitative analysis of the electroencephalogram (EEG) to explore the mechanisms underlying opioid effects on arousal and the sleep-wake cycle, and to relate these effects to behavioral measures of nociception and reinforcement. Computerized methods for quantitative EEG analysis will be used to characterize drug dependence and self-administration in alert, freely-moving rats. Drug effects will be observed after either intravenous or intracerebroventricular infusions, in animals maintained with chronic cortical electrodes for EEG recording. In preliminary studies, low doses of the opioid agonist morphine have been shown to produce an alert EEG pattern with little slow wave activity.' This is described as a desynchronized EEG, and is reflected by reduced total spectral power. Treatment with opioid antagonist naloxone increases the amount of slow wave activity in the EEG, resulting in greater total spectral power. When a series of morphine infusions are self-administered as a reinforcer, reductions in EEG total spectral power occur to a greater extent than in subjects that passively receive the same pattern of infusions. Additional research is proposed in the following areas: l. Opioid Receptor Selectivity. Desynchronization of the EEG after treatment with low doses of opioid agonists is centrally mediated, through mu opioid receptors, with participation of cholinergic mechanisms. 2. Reinforcement. Theta rhythms generated in the hippocampus will be related to opioid reinforcing effects. EEC correlates of morphine self- administration will be compared with qualitatively different reinforcers. 3. Nociception. Quantitative EEC changes during morphine self- administration will be related to predrug levels of nociception and responsiveness to opioid blockade.